Fat Accumulation In Humans Research Articles

Serum Retinol-Binding Protein-4, Leptin, and Adiponectin Concentrations Are Related to Ectopic Fat Accumulation

Serum retinol-binding protein 4 (RBP-4), leptin, and adiponectin concentrations identify insulin resistance in varied conditions, but their relationships with insulin sensitivity and ectopic fat accumulation are unclear. Our objective was to establish how these adipokines are related with intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. We assessed retrospectively serum fasting RBP-4 concentrations in 1) 53 nondiabetic individuals in which insulin sensitivity and IMCL content were assessed by means of the insulin clamp and of 1H magnetic resonance spectroscopy of the calf muscles, and 2) 140 nondiabetic individuals in which insulin sensitivity and the IHL content were assessed by means of the updated homeostasis model assessment and of 1H magnetic resonance spectroscopy. In both experiments, serum leptin and adiponectin concentrations were measured. Fasting serum RBP-4, adiponectin, and leptin were associated with peripheral insulin sensitivity, were abnormal in the first-degree relatives of type 2 diabetic parents, and correlated with the soleus IMCL content and with the IHL content. The association of RBP-4 and adiponectin with insulin sensitivity was age, sex, and body mass index independent, but stepwise regression analysis suggested that RBP-4, but not adiponectin and leptin, was independently associated with insulin sensitivity. Adiponectin was independently associated with the IHL content, RBP-4, and leptin with the soleus IMCL content. Serum RBP-4 was a robust marker of insulin resistance. Serum RBP-4, leptin, and adiponectin concentrations reflected ectopic fat accumulation in humans.

Effect of Randomly Interesterified Triacylglycerols Containing Medium- and Long-Chain Fatty Acids on Energy Expenditure and Hepatic Fatty Acid Metabolism in Rats

In our previous studies, medium- and long-chain triacylglycerols (MLCT), randomly interesterified triacylglycerols containing medium-chain and long-chain fatty acids in the same glycerol molecule, significantly reduced body fat accumulation in humans and rats. To clarify mechanism(s) for this effect of MLCT, we measured energy expenditure and hepatic fatty acid metabolism in rats by comparison with long-chain triacylglycerols (LCT) or medium-chain triacylglycerols (MCT). MLCT, compared with LCT, showed significantly lower body fat accumulation, higher 24-h energy expenditure and acyl-CoA dehydrogenase activity measured using octanoyl-CoA as a substrate, and similar lipogenic activity. MCT, compared with LCT, showed significantly higher energy expenditure, but fat accumulation was comparable. Additionally, MCT exhibited significantly higher lipogenic activity than the other oils. These data suggest that enhancement of energy expenditure and medium-chain fatty acids (MCFA) oxidation without activating de novo lipogenesis are responsible at least for the lower body fat accumulation in rats fed MLCT. The activation of hepatic lipogenesis by excessive intake of MCFA might counteract their preventive effects on body fat accumulation.

Dietary diacylglycerol suppresses high fat diet-induced hepatic fat accumulation and microsomal triacylglycerol transfer protein activity in rats

We have recently shown that the long-term ingestion of dietary diacylglycerol (DAG) mainly containing 1,3-isoform reduces body fat accumulation in humans as compared to triacylglycerol (TAG) with the same fatty acid composition. The fat reduction in this human experiment was most pronounced in visceral fat and hepatic fat. Recent animal studies have also indicated that dietary DAG induces alteration of lipid metabolism in the rat liver. In the present study, the dietary effects of DAG on high fat diet-induced hepatic fat accumulation and hepatic microsomal triglyceride transfer protein (MTP) activity were examined in comparison with those of TAG diet in rats. When the TAG oil content was increased from 10 to 30 g/100 g diet, hepatic TAG concentration, hepatic MTP activity and MTP large subunit mRNA levels were significantly increased after 21 days. However, when the dietary TAG oil (30 g/100 g diet) was replaced with the same concentration of DAG oil with the same fatty acid composition, the increase of the TAG concentration and the MTP activity in the liver were significantly less and the mRNA levels remained unchanged. The MTP activity levels correlated significantly with hepatic TAG concentration. These results showed that dietary DAG may suppress high fat diet-induced MTP activity in the liver, and indicated the possibility that hepatic TAG concentration may regulate hepatic MTP activity.

ガルシニアエキス長期投与による人の内臓脂肪蓄積への影響 プラセボ二重盲検比較試験（原標題は英語）

(−)-Hydroxycitric acid (HCA), an active ingredient extracted from the rind of the Indian fruit Garcinia cambogia inhibits ATP-citrate lyase and is used for anti-obesity treatment. This study was conducted to examine the long-term effects of G. cambogia extracts on body fat accumulation in humans who are preobese or obese class 1 (body mass index from 25 to 35 kg/m2). A total of 40 subjects were randomized to either a G. cambogia (n=20, 1000 mg of HCA per day) or a placebo (n=20) group. The treatment period was 8 weeks. Each was subjected to computed tomography (CT) scan at the umbilical level before and after the treatment period, and blood samples taken to measure the clinical laboratory data every 4 weeks. As for a higher visceral fat area (VFA) in the subjects (with an initial VFA over 90 cm2), both the VFA and VFA/SFA (subcutaneous fat area) ratio in the G. cambogia group significantly decreased, compared to the placebo group (p<0.01 and p<0.05, respectively). Triacylglycerol was also reduced significantly in higher VFA subjects in the G. cambogia group, compared to the initial levels (p=0.05), but there were no significant difference between the groups in loss of body weight and the waist-hip ratio. No adverse effect was observed through out the test period. In conclusion, G. cambogia extract is useful for reducing body fat accumulation, especially visceral fat accumulation.

Plasma plasminogen activator inhibitor-I is associated with plasma leptin irrespective of body mass index, body fat mass, and plasma insulin and metabolic parameters in premenopausal women

Leptin, the satiety hormone expressed almost exclusively in adipose tissue, is a marker of body fat accumulation in humans. Recent studies have shown that plasminogen activator inhibitor-1 (PAI-1), a prothrombotic factor associated with atherosclerosis complications, is also produced in adipose tissue. The objective of the present study was to determine whether PAI-1 antigen plasma concentrations are associated with leptin plasma levels or the body fat mass (FM) independently of the variables known to influence PAI-1 production. Sixty-one nondiabetic women aged 18 to 45 years with a wide range of values for the body mass index ([BMI] 18.1 to 37.7 kg/m 2) were evaluated for (1) body FM and fasting plasma levels of (2) PAI-1 antigen, (3) PAI-1 activity, (4) leptin, (5) insulin, (6) blood glucose, and (7) lipids (cholesterol, high-density lipoprotein [HDL]-cholesterol, and triglycerides [TG]). Body FM and fat-free mass (FFM) were estimated during fasting conditions by the bioimpedance analysis (BIA) method using a tetrapolar device. Body fat distribution was evaluated by the waist circumference and the waist to hip ratio (WHR). FM was directly associated with both PAI-1 antigen ( r = .585, P < .001) and PAI-1 activity ( r = .339, P < .001). Seemingly, leptin was positively related to both PAI-1 antigen ( r = .630, P < .001) and PAI-1 activity ( r = .497, P < .001). Moreover, both PAI-1 antigen and PAI-1 activity were directly correlated with FFM ( r = .285, P < .05, and r = .336, P < .01, respectively), BMI ( r = .594, P < .001, and r = .458, P < .001, respectively), and WHR ( r = .510, P < .001, and r = .391, P < .005, respectively). Insulin was directly related to PAI-1 antigen ( r = .540, P < .001), PAI-1 activity ( r = .259, P < .05), leptin ( r = .447, P < .001), and FM ( r = .435, P < .001). The association between PAI-1 antigen (dependent variable) and leptin or FM was tested by a stepwise regression model simultaneously including leptin, FM, BMI, WHR, age, FFM, and fasting insulin, blood glucose, TG, cholesterol, and HDL-cholesterol as independent variables. PAI-1 antigen maintained a significant positive independent relationship only with leptin ( t = 2.923, P < .01), insulin ( t = 3.489, P < .001), and fasting blood glucose ( t = 2.092, P < .05), and a negative independent relationship with HDL-cholesterol ( t = −2.634, P < .05). In conclusion, the strong relationship between PAI-1 antigen and leptin irrespective of other variables known to influence these factors seems to indicate that leptin per se may potentially increase PAI-1 plasma concentrations in obese subjects.

Effect of lipectomy and long-term dexamethasone on visceral fat and metabolic variables in rats

Intraperitoneal (IP) fat accumulation in humans is a risk factor for a number of diseases. We tried to increase this particular adipose mass in rats by long-term administration of low-dose dexamethasone (Dex) and/or elimination of other fat depots. Male adult Wistar rats were lipectomized (Lip) or sham-operated (Sh). Bilateral lipectomy of retroperitoneal and inguinal fat pads was performed under anesthesia with Na pentobarbital 40 mg/kg supplemented with ether. After 8 days, half the animals of each group received Dex in their drinking water (0.1 μg/mL) while the other half received water (W), for a total of four groups: Sh-W, Lip-W, Sh-Dex, and Lip-Dex. Body weight (BW) and food and water intake were measured throughout the treatment period. A glucose tolerance test was performed 34 days after starting Dex treatment, and then rats were killed, fat depots were weighed, and plasma and liver were obtained for metabolic determinations. Dex rats ate the same amount of food as W controls, but gained significantly less weight (2.02 ± 0.18 v 3.82 ± 0.10 g/d, P < .01). Mean daily W intake was approximately 40 mL/d in all groups, which means that Dex rats ingested approximately 4 μg/d Dex. Average glycemic values during the 180-minute glucose tolerance test were as follows: Sh-W, 162 ± 13; Lip-W, 166 ± 7; Sh-Dex, 118 ± 6; and Lip-Dex, 229 ± 27 mg/dL. These values show that glucose tolerance was improved by Dex treatment alone, but was impaired in Lip-Dex animals. The same trend was evident for the relative weights (percent of BW) of two intact adipose depots: IP and epididymal (EPI) (Sh-W, 2.08 ± 0.13 and 1.35 ± 0.11, respectively; Lip-W, 1.67 ± 0.15 and 1.17 ± 0.11; Sh-Dex, 1.66 ± 0.10 and 1.28 ± 0.07; Lip-Dex, 2.41 ± 0.11 and 1.53 ± 0.09). Average glycemia for all rats was significantly correlated with IP ( r = .55, P < .01) but not with EPI; moreover, it was also correlated in the Sh-W control group ( r = .81, P < .05), suggesting a normal relation between these variables. Liver triglycerides (LTG), which were elevated in Dex rats, were also correlated with IP ( r = .51, P < .02 for all rats and r = .82, P < .05 for Sh-W rats). The results show that long-term administration of low-dose Dex has some different effects in normal versus Lip rats concerning mainly the IP fat depot, the relative mass of which seems to significantly affect glucose tolerance.